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Differentiation; Research in Biological... Oct 2011In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of... (Review)
Review
In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences.
Topics: Adenocarcinoma, Clear Cell; Animals; Cell Differentiation; Cervix Uteri; Diethylstilbestrol; Epithelial Cells; Estrogens, Non-Steroidal; Female; Humans; Mesoderm; Metaplasia; Mullerian Ducts; Organogenesis; Uterine Neoplasms; Uterus; Vagina
PubMed: 21612855
DOI: 10.1016/j.diff.2011.04.008 -
Oncology (Williston Park, N.Y.) Sep 2022A 40-year-old unmarried Brazilian woman, Ms A, received a diagnosis of papillary renal cell carcinoma (RCC) in February 2020; she underwent nephrectomy the following...
A 40-year-old unmarried Brazilian woman, Ms A, received a diagnosis of papillary renal cell carcinoma (RCC) in February 2020; she underwent nephrectomy the following month. In August, she began to experience generalized pain with subsequent scans revealing metastatic disease to the supraclavicular lymph node, liver, and vagina. In October 2020, Ms A started first-line systemic combination treatment with nivolumab (Opdivo; 3 mg/kg) plus ipilimumab (Yervoy; 1 mg/kg) every 3 weeks for 4 doses, followed by nivolumab (3 mg/kg) every 2 weeks, to be taken for 2 years. In April 2021, follow-up testing revealed a partial response to therapy, and a complete response was evident in August 2021. Ms A was first screened for biopsychosocial distress by the supportive care team in October 2020, and she completed the Edmonton Symptom Assessment System (ESAS) evaluation.During her fourth cycle of treatment in October 2020, the patient was assessed with the ESAS. During her medical visits, Ms A also expressed concern regarding her physical symptoms and admitted frequent self-monitoring for signs of recurrence or progression. Her oncologist prescribed tramadol for pain and the supportive care team recommended increased engagement in physical activity. Upon further assessment, the patient reported a belief that her psychosocial symptoms, worry about recurrence or progression, and time spent self-monitoring were a normal part of her cancer experience.
Topics: Adult; Carcinoma, Renal Cell; Female; Humans; Ipilimumab; Kidney Neoplasms; Nivolumab; Pain; Psycho-Oncology; Tramadol
PubMed: 36107784
DOI: 10.46883/2022.25920972 -
Oncology Letters Feb 2021Primitive neuroectodermal tumor (PNT) and Ewing's sarcoma are rare, round-cell tumors, characterized by the presence of the t(11; 22)(q24; q12) chromosomal... (Review)
Review
Primitive neuroectodermal tumor (PNT) and Ewing's sarcoma are rare, round-cell tumors, characterized by the presence of the t(11; 22)(q24; q12) chromosomal translocation. A review of the literature revealed only 38 previously reported cases of vulvar PNT and Ewing's sarcoma and 15 vaginal PNT and Ewing's sarcoma. Although rare, these types of tumors should be taken into consideration when making a differential diagnosis for vulvar or vaginal tumors. The currently available data is limited, and therefore, case reports are essential for improving knowledge and management of these types of extremely rare tumors. However, further molecular and histopathological studies are essential for an improved understanding of these conditions and for an early, correct diagnosis. Although the gathered and presented data from the present review are limited, the literature demonstrates that the outcome of these types of cancer are more favorable compared with outcomes observed for carcinomas in more typical locations.
PubMed: 33552288
DOI: 10.3892/ol.2021.12432 -
International Journal of Environmental... Nov 2022We report a case of a 76-year-old female with a stage IB, grade I endometrioid endometrial carcinoma who presented with right-hip pain and an enlarging black, exophytic,...
CASE
We report a case of a 76-year-old female with a stage IB, grade I endometrioid endometrial carcinoma who presented with right-hip pain and an enlarging black, exophytic, subungual lesion on her right-small-finger distal phalanx. Clinically, the distal phalanx lesion was suspicious for a subungual melanoma; however, advanced imaging suggested metastatic disease, with lesions in the acetabulum, lungs, brain, vulva, and vagina.
CONCLUSION
Partial amputation of the right, small finger and vulvar biopsies confirmed an endometrial carcinoma. To our knowledge, this is the first described case of endometrial adenocarcinoma metastasis to the phalanx of an upper extremity, mimicking a subungual melanoma.
Topics: Humans; Female; Aged; Carcinoma, Endometrioid; Melanoma; Endometrial Neoplasms; Adenocarcinoma; Nail Diseases
PubMed: 36361369
DOI: 10.3390/ijerph192114494 -
Acta Cirurgica Brasileira 2007To establish an inoculation model of Walker 256 carcinoma on cervix uteri and vagina of rats.
PURPOSE
To establish an inoculation model of Walker 256 carcinoma on cervix uteri and vagina of rats.
METHODS
Fifteen female rats were used, and assigned to three groups each one with five rats: group A - rats with 4 x 10(6) cells of Walker 256 carcinoma without acid acetic inoculation; group B - rats with 2 x 10(6) cells of Walker 256 carcinoma with acid acetic inoculation and group C: rats with 4 x 10(6) cells of Walker 256 carcinoma with acid acetic inoculation. The day before tumor cells inoculation the rats from groups B and C were anaesthetized with diethylether and 0,3 ml of acetic acid was inoculated into their vaginas. Tumor cell inoculation into the vagina and cervix was done under general anesthesia with diethylether. Then a endocervical brush was used to scrape the vaginal wall and after that 0,3 ml of the liquid containing tumor cells was inoculated on the vagina and cervix. For the tumor analysis, animals were euthanized at day 12 following tumor cell implantation by an excessive inhalation of diethylether. Tumor was resected entirely and weighed and the tumors were then sectioned and counter stained with hematoxylin and eosin for histopathologic evaluation. It was also calculated the percentage of tumor equivalent to the body weight by the formula: P= tumor weight / body weight x 100. Data were analyzed by one-way analysis of variance - ANOVA. P values < 0.05 were taken to indicate statistical significance.
RESULTS
Implantation and growth on GB and GC was 100% and on GA 20%. There was no statistical difference between GB and GC averages.
CONCLUSION
According to the methods used, the Walker 256 carcinoma inoculation model into vagina and cervix have an implantation and growth rate of 100% when associated with previous acid acetic inoculation and there is no behavioral difference between using 2 x 10(6) or 4 x 10(6) cells on its inoculation.
Topics: Animals; Carcinoma 256, Walker; Disease Models, Animal; Female; Neoplasm Transplantation; Rats; Rats, Wistar; Uterine Cervical Neoplasms; Vaginal Neoplasms
PubMed: 18235940
DOI: 10.1590/s0102-86502007000600014 -
Journal of Contemporary Brachytherapy Jun 2013To report the outcomes of patients receiving vaginal brachytherapy and/or external beam radiation therapy (EBRT) for primary vaginal cancer.
PURPOSE
To report the outcomes of patients receiving vaginal brachytherapy and/or external beam radiation therapy (EBRT) for primary vaginal cancer.
MATERIAL AND METHODS
Between 1983 and 2009, 63 patients received brachytherapy and/or EBRT for primary tumors of the vagina at a single tertiary center. Patient data was collected via chart review. The Kaplan-Meier method was used to calculate actuarial pelvic local control (LC), disease-free survival (DFS), overall survival (OS), and severe late toxicity rates. Acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3 (CTCAE v3.0).
RESULTS
Median follow up was 44.2 months. Patients with early stage disease (stages I and II) had significantly improved 5-year OS when compared to patients with locally advanced disease (stages III and IVA) (73.3 vs. 34.4%, p = 0.032). Patients with greater than 1/3 vaginal involvement had significantly worse prognosis than patients with tumors involving 1/3 or less of the vagina, with the later having superior DFS (84.0 vs. 52.4%, p = 0.007) and LC (86.9 vs. 60.4%, p = 0.018) at 5-years. Age, histology, and brachytherapy technique did not impact treatment outcomes. The 5-year actuarial grade 3 or higher toxicity rate was 23.1% (95% CI: 10.6-35.6%). Concurrent chemotherapy had no impact on outcomes or toxicity in this analysis.
CONCLUSIONS
Success of treatment for vaginal cancer depends primarily on disease stage, but other contributing factors such as extent of vaginal involvement and tumor location significantly impact outcomes. Treatment of vaginal cancer with primary radiotherapy yields acceptable results with reasonable toxicity rates. Management of this rare malignancy requires a multidisciplinary approach to appropriately optimize therapy.
PubMed: 23878551
DOI: 10.5114/jcb.2013.36177 -
Differentiation; Research in Biological... Oct 2012Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well... (Review)
Review
Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow-up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models that can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses their molecular pathogenesis.
Topics: Adenocarcinoma, Clear Cell; Animals; Diethylstilbestrol; Estrogens, Non-Steroidal; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Phosphoproteins; Pregnancy; Prenatal Exposure Delayed Effects; Trans-Activators; Uterine Cervical Neoplasms; Vaginal Neoplasms
PubMed: 22682699
DOI: 10.1016/j.diff.2012.05.004 -
Cancer Research Communications Jun 2022The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial...
The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.
Topics: Humans; Female; Endometrial Neoplasms; Vagina; Hysterectomy; Microbiota; Carcinoma
PubMed: 35928983
DOI: 10.1158/2767-9764.CRC-22-0075 -
International Journal of Cancer Apr 2009This meta-analysis investigated human papillomavirus (HPV) prevalence in vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3 and carcinoma... (Meta-Analysis)
Meta-Analysis
This meta-analysis investigated human papillomavirus (HPV) prevalence in vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3 and carcinoma from 93 studies conducted in 4 continents and using PCR assays. Overall HPV prevalence was 67.8%, 85.3% and 40.4% among 90 VIN1, 1,061 VIN2/3 and 1,873 vulvar carcinomas; 100%, 90.1% and 69.9% among 107 VAIN1, 191 VAIN2/3 and 136 vaginal carcinomas; and 91.5%, 93.9% and 84.3% among 671 AIN1, 609 AIN2/3 and 955 anal carcinomas, respectively. HPV16 was found more frequently (>75%) and HPV18 less frequently (<10%) in HPV-positive vulvar, vaginal and anal carcinomas than in cervical carcinoma. HPV6 and 11 were common in VIN1 and AIN1, but not in VAIN1. HPV prevalence in vulvar carcinoma varied most by histological type (69.4% in warty-basaloid and 13.2% in keratinized type) and was also higher in women 60 years or younger and in studies carried out in North America. HPV prevalence in anal carcinoma was higher among women (90.8%) than men (74.9%), but no difference by gender emerged in North America. The majority of AIN2/3 derived from studies of HIV-positive individuals and/or men who have sex with men. Among AIN2/3, HIV infection was associated with higher HPV prevalence, more multiple-type infections and a relative under-representation of HPV16. In conclusion, approximately 40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be avoided by prophylactic vaccines against HPV16/18. This proportion would be similar for the corresponding high-grade lesions of the vagina and anus, but higher for VIN2/3 (75%) than for vulvar carcinoma.
Topics: Anus Neoplasms; Female; HIV Infections; Humans; Male; Papillomavirus Infections; Prevalence; Vaginal Neoplasms; Vulvar Neoplasms
PubMed: 19115209
DOI: 10.1002/ijc.24116 -
Medicine May 2024The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV... (Review)
Review
The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV infections occur asymptomatically and resolve spontaneously. However, infection with high-risk viral strains can lead to the development of preneoplastic lesions, with an increased propensity to become cancerous. The location of these malignancies includes the oral cavity, cervix, vagina, anus, and vulva, among others. The role of HPV in carcinogenesis has already been demonstrated for the aforementioned neoplasia. However, regarding skin malignancies, the mechanisms that pinpoint the role played by HPV in their initiation and progression still elude our sight. Until now, the only fully understood mechanism of viral cutaneous oncogenesis is that of human herpes virus 8 infection in Kaposi sarcoma. In the case of HPV infection, however, most data focus on the role that beta strains exhibit in the oncogenesis of cutaneous squamous cell carcinoma (cSCC), along with ultraviolet radiation (UVR) and other environmental or genetic factors. However, recent epidemiological investigations have highlighted that HPV could also trigger the onset of other non-melanocytic, for example, basal cell carcinoma (BCC), and/or melanocytic skin cancers, for example, melanoma. Herein, we provide an overview of the role played by HPV in benign and malignant skin lesions with a particular focus on the main epidemiological, pathophysiological, and molecular aspects delineating the involvement of HPV in skin cancers.
Topics: Humans; Skin Neoplasms; Papillomavirus Infections; Papillomaviridae; Carcinoma, Squamous Cell; Carcinoma, Basal Cell; Melanoma; Human Papillomavirus Viruses
PubMed: 38787972
DOI: 10.1097/MD.0000000000038202